SLIT-ROBO Rho GTPase-activating protein 2C

Human-specific protein that acts as a key modifier of cortical connectivity in the human brain. Acts by inhibiting the functions of ancestral paralog SRGAP2/SRGAP2A, a postsynaptic protein that regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons. SRGAP2C is unstable but is able to heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A levels through proteasome-dependent degradation. Inhibition of SRGAP2/SRGAP2A by SRGAP2C leads to an increase in synaptic density and protracted synaptic maturation of both excitatory and inhibitory synapses. Modifies cortical circuit connectivity by increasing the number of local and long-range cortical inputs received by layer 2/3 pyramidal neurons. Also able to increase the probability of sensory-evoked responses by layer 2/3 pyramidal neurons.